Dietary inflammatory index could increase the risk of sarcopenia in patients with chronic kidney disease

Using a system that incorporates a variety of food items rather than focusing on individual components can aid in assessing the inflammatory effects of a diet on disease outcomes such as chronic kidney disease (CKD). Therefore, we decided to investigate the association between dietary inflammatory index (DII) and the risk of protein–energy wasting (PEW) and sarcopenia in patients with CKD. In this cross-sectional study, 109 patients with CKD were selected from two clinics in Shiraz, Iran. The intake of individuals’ diets was recorded using a validated 168-item food frequency questionnaire. Additionally, Asian Working Group for Sarcopenia (AWGS) guidelines were utilized to evaluate muscles’ strength, mass, and function. Also, four International Society of Renal Nutrition and Metabolism (ISRNM) criteria (body mass index, intake of protein, albumin, and urine creatinine) were used to diagnose PEW. Logistic regression was used to assess the association between DII and sarcopenia as well as PEW. The results showed that the intake of saturated fatty acids, trans fatty acids, niacin, beta-carotene, and vitamin C was significantly different between lower and higher DII groups. In the univariate model, higher odds of sarcopenia was observed by each unit increase in DII (odds ratio (OR) = 1.379, 95% confidence interval (CI): 1.042–1.824) and age (OR = 1.073, 95% CI: 1.017–1.132). Additionally, in the multivariate model, the association between DII and age with odds of sarcopenia remained significant (DII: OR = 1.379, 95% CI: 1.030–1.846 and age: OR = 1.063, 95% CI: 1.007–1.121). The current study suggests the possible role of pro-inflammatory foods in worsening muscle health, specifically sarcopenia, in CKD patients. Future longitudinal studies may reveal the causative nature of these correlations.


Data collection
The percentage of muscle and fat mass was assessed by bioelectrical impedance analysis (BIA).Participants' weight was measured with a precision of 0.1 kg, and the height and mid-arm circumference (MAC) were determined with an accuracy of 0.5 cm.Also, body mass index (BMI) was calculated.Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ) 28 .For evaluation of biochemical variables, 5 mL blood samples were collected from each participants.

Sarcopenia and PEW diagnosis
The Asian Working Group for Sarcopenia (AWGS) guidelines were utilized to evaluate muscle strength, mass, and function 29,30 .Handgrip strength (HGS) was measured using a dynamometer to assess muscle strength.Muscle function was evaluated using gait speed (walking speed in 6 m) and the five-time chair-stand test.Skeletal muscle mass index (SMI) was calculated as skeletal muscle mass divided by the square of height.The criteria for the diagnosis of sarcopenia were as follows: SMI < 7 kg/m 2 for men or SMI < 5.7 kg/m 2 for women was the first criterion.Additionally, a gait speed of fewer than 1 m/s or more than 12 s in the five-time chair-stand test, and/ or an HGS of less than 28 kg for men and 18 kg for women, were used to confirm the diagnosis of sarcopenia 29,30 .
According to the International Society of Renal Nutrition and Metabolism (ISRNM), four criteria were used to distinguish PEW: BMI < 23 kg/m 2 , protein intake < 0.6 g/kg/day, biochemical parameters such as albumin < 3.8 g/ dL, and lower quartile of urine creatinine excretion (UCE) in 24 h based on sex.PEW was defined as meeting three or more of these criteria 31 .

Dietary assessment
The intake of individuals' diets was recorded using a validated 168-item food frequency questionnaire (FFQ) 32 .After calculating food grams and multiplying by the daily intake frequency, the amount of each item was determined.FFQ was used to calculate the DII.Initially, the residual method was employed to adjust energy intake for each nutrient 33 .The DII score was determined according to the method described by Shivappa et al. 34 .To calculate DII, 31 food parameters were considered, including energy, fat, protein, carbohydrates, various vitamins (B 1 , B 2 , B 3 , B 6 , B 9 , B 12 , C, A, D, and E), beta-carotene, fiber, trans fatty acid (TFA), cholesterol, saturated fatty acid (SFA), polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), iron, selenium, magnesium, zinc, omega-6, omega-3, caffeine, onion, garlic, and tea.
For each participant, a Z-score was calculated by subtracting the mean of the global standard from the amount consumed and dividing it by the global standard deviation (SD).This Z-score was then converted to a percentile, multiplied by two, and adjusted by subtracting one, to minimize the influence of outliers.Additionally, this value was multiplied by the corresponding food inflammatory effect score to obtain the specific DII score for each food parameter.Finally, the overall DII score was calculated by summing all these individual scores.A higher DII score indicates a higher pro-inflammatory potential of the diet.

Statistical analysis
For statistical analysis, SPSS software (version 22) was used.Continuous variables were described using mean ± SD or median (interquartile range (IQR)), while categorical variables were presented as percentages.An independent sample T-test assessed parametric continuous variables, whereas the Mann-Whitney test was employed for non-parametric continuous variables.The chi-square test was applied for categorical variables.Additionally, logistic regression was conducted to assess the association between DII and sarcopenia as well as PEW.The multivariate model was adjusted for age, energy, protein, fat, and salt intake, sex and smoking history.Statistical significance was defined as a p-value less than 0.05.

Ethics approval and consent to participate
This study was approved by the medical research and ethics committee of Shiraz University of Medical Science and the informed consents were completed by all participants.

Results
The baseline features of the study population, according to the lower and higher mean of DII, are reported in Table 1.The median total iron-binding capacity (TIBC) (P = 0.031) and the DII total score (P˂0.001) were significantly greater in the higher DII group compared to the lower DII group.Other variables did not show significant differences between the two groups.
The intake of DII components based on lower and higher than the mean DII is shown in Table 2.According to the table, SFA (P = 0.001), TFA (P = 0.017), niacin (P = 0.036), beta-carotene (P = 0.005), and vitamin C (P = 0.033) were significantly different between the two groups.
The association between the DII score and the odds of sarcopenia in univariate and multivariate models is shown in Table 3.In the univariate model, a significant increase in the odds of sarcopenia was observed with each unit increase in DII (odds ratio (OR) = 1.379, 95% confidence interval (CI): 1.042-1.824)and age (OR = 1.073, 95% CI: 1.017-1.132).In the multivariate model, the association between DII and age with the odds of sarcopenia remained significant (DII: OR = 1.379, 95% CI: 1.030-1.846and age: OR = 1.063, 95% CI: 1.007-1.121).
The association between the DII score and the odds of PEW in univariate and multivariate models is shown in Table 4.In both models, no significant association was observed.

Discussion
The main finding of our study was the significant association between a higher DII score and an increased risk of sarcopenia in CKD patients.Dietary inflammation appears to compromise muscle health in these patients.Contrary to expectations, our results did not show a significant association between DII scores and PEW.
Inflammation is common in patients with CKD, and the level of inflammation increases as kidney function worsens.Impaired kidney function results in the accumulation of uremic toxins, which exacerbate inflammatory states 35 .Elevated inflammatory markers, including C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-α), exacerbate muscle protein catabolism, contributing to sarcopenia 36 .Antiinflammatory interventions have shown promise in reducing CKD progression and attenuating sarcopenia 37,38 .These approaches attempt to disrupt the harmful loop that connects CKD and sarcopenia by targeting inflammation and providing a potential therapeutic tool to enhance the quality of life for CKD patients.Our findings revealed that a lower DII score was associated with less sarcopenia.This finding aligns with previous studies that have reported a positive association between DII and muscle mass in children, as well as sarcopenia in patients with CKD and Crohn's disease [39][40][41] .
A pro-inflammatory diet may cause muscle mass loss by intensifying systemic inflammation 12 , and protective dietary patterns should be considered as a modifiable preventive factor for CKD-related sarcopenia.The DII, a novel dietary index that determines the total inflammatory potential of a diet, has been validated against systemic inflammatory biomarkers 42 .The DII score considers how various foods and nutrients interact with each other, rather than examining each nutrient or food independently concerning the disease.Consequently, it may offer more promising methods for disease prevention and control 43,44 .
There are several potential mechanisms explaining how high-inflammatory diets can exacerbate sarcopenia.A pro-inflammatory diet may heighten systemic inflammation, resulting in elevated levels of cytokines that inhibit muscle protein synthesis 40 .This can harm muscular health and increase oxidative stress, insulin resistance, and nutrient deficiencies 45,46 .Additionally, a pro-inflammatory diet may affect the gut flora, leading to muscle wasting by impairing the absorption of nutrients essential for muscle health and increasing systemic inflammation and insulin resistance 47 .
The present study did not show a significant association between DII and PEW.Few studies have investigated this association in CKD patients.However, a cross-sectional study of 105 subjects with ESRD did show associations between PEW and a pro-inflammatory diet 48 .One explanation for this discrepancy is that participants www.nature.com/scientificreports/ in our study were in the moderate stage of CKD, while the mentioned study examined ESRD.The prevalence of PEW in stages 3-5 is 11-46%, whereas in dialysis patients, it ranges from 28 to 80% 49 .The results may have also been impacted by methodological considerations such as sample size, PEW measurement techniques, or other confounding variables.It is also conceivable that, despite certain areas of overlap, the mechanisms behind sarcopenia and PEW have significant differences 50,51 , and DII might affect only a subset of these pathways.Further research is required to understand the underlying causes of this unequal connection and to consider other potential confounding factors.
In the present study, we observed that levels of SFA and TFA increased, and the levels of niacin, beta-carotene, and vitamin C decreased with an increase in the DII score.Additionally, the DII score was positively associated Table 1.Baseline characteristics of the study participants across the median of DII.BMI: body mass index, MAC: mid-arm circumference, ASM: appendicular skeletal muscle mass, HGS: handgrip strength, PEW: protein-energy wasting, SGA: subjective global assessment, ALT: alanine transaminase, AST: aspartate transaminase, PTH: parathyroid hormone, GFR: glomerular filtration rate, TIBC: total iron-binding capacity, BUN: blood urea nitrogen, FBS: fasting blood sugar, TG: triglyceride, LDL-C: low-density lipoprotein cholesterol, HDL-C: high-density lipoprotein cholesterol, PCO2: partial pressure of carbon dioxide, PO 2 : partial pressure of oxygen, DII: dietary inflammatory index, M: median.Values are mean ± SD or median (IQR) for continuous and percentage for categorical variables. 1Using Mann-Whitney U test for nonparametric variables. 2Using independent sample T-test for parametric variables. 3Using chi-square test for categorical variables.Significant values are in bold.

Lower than mean (n = 56) Higher than mean (n = 53) P-value
Age (year) 1 64.www.nature.com/scientificreports/with sarcopenia status.These components have previously been linked to inflammatory responses in CKD patients.For example, high intakes of SFA and TFA are associated with pro-inflammatory markers and muscle mass 52,53 .Conversely, nutrients such as beta-carotene and vitamin C possess anti-inflammatory and musclebuilding properties [54][55][56] .Although these nutrients were consumed around the recommended dietary allowance (RDA), research has indicated that patients experienced better outcomes when supplemented with nutrients 56,57 .However, more studies are needed to evaluate the safety and effectiveness of combined supplementation of antiinflammatory nutrients.Furthermore, diets that replace SFA and TFA with healthier MUFA and PUFA have been shown to reduce inflammation levels 52,58 and have positive effects on animal muscles.However, clinical trials have yielded contradictory results regarding their impact on muscles, necessitating further research 52 .
Although the current study provides insightful findings, it is important to acknowledge potential limitations.Due to the cross-sectional nature of our study, longitudinal studies are still needed to confirm causation and evaluate the long-term effects of diet modification in CKD patients.Also, further research is necessary to elucidate mechanistic pathways linking dietary inflammation to CKD outcomes.Such studies could inform the development of nutritional therapies tailored specifically to the requirements of CKD patients.
Another limitation of the present study was the small sample size.Furthermore, nutrient intake was assessed using the FFQ, which may introduce recall bias.Moreover, certain confounding variables were not controlled for in our study.

Conclusions
The current study highlighted the possible role of pro-inflammatory foods in exacerbating muscle health issues, specifically sarcopenia, in CKD patients.Future longitudinal studies could elucidate the causal relationships of these associations and potentially facilitate the development of nutritional therapies aimed at mitigating musclerelated problems in CKD. https://doi.org/10.1038/s41598-024-65340-6

Table 3 .
Association between the dietary inflammatory index and the odds of sarcopenia in two uni-and multivariate models.OR, odds ratio; CI, confident interval; DII, dietary inflammatory index; Ref, reference.Obtained from logistic regression and using enter method for multivariate analysis.These values are odds ratios (95% CIs).Significant values are shown in bold.

Table 4 .
Association between the dietary inflammatory index and the odds of protein-energy wasting in two uni-and multivariate models.OR, odds ratio; CI, confident interval; DII, dietary inflammatory index; Ref, reference.Obtained from logistic regression and using enter method for multivariate analysis.These values are odds ratios (95% CIs).Significant values are shown in bold.